rs17003235
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_025074.7(FRAS1):c.6444C>T(p.Thr2148=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,613,304 control chromosomes in the GnomAD database, including 37,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.21 ( 3651 hom., cov: 32)
Exomes 𝑓: 0.21 ( 34198 hom. )
Consequence
FRAS1
NM_025074.7 synonymous
NM_025074.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.561
Genes affected
FRAS1 (HGNC:19185): (Fraser extracellular matrix complex subunit 1) This gene encodes an extracellular matrix protein that appears to function in the regulation of epidermal-basement membrane adhesion and organogenesis during development. Mutations in this gene cause Fraser syndrome, a multisystem malformation that can include craniofacial, urogenital and respiratory system abnormalities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
?
Variant 4-78450320-C-T is Benign according to our data. Variant chr4-78450320-C-T is described in ClinVar as [Benign]. Clinvar id is 261809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-78450320-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.561 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FRAS1 | NM_025074.7 | c.6444C>T | p.Thr2148= | synonymous_variant | 45/74 | ENST00000512123.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FRAS1 | ENST00000512123.4 | c.6444C>T | p.Thr2148= | synonymous_variant | 45/74 | 5 | NM_025074.7 | P1 | |
FRAS1 | ENST00000682513.1 | c.6444C>T | p.Thr2148= | synonymous_variant | 45/64 | ||||
FRAS1 | ENST00000684159.1 | c.6444C>T | p.Thr2148= | synonymous_variant | 45/45 |
Frequencies
GnomAD3 genomes ? AF: 0.210 AC: 31858AN: 151920Hom.: 3653 Cov.: 32
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GnomAD3 exomes AF: 0.163 AC: 40697AN: 249132Hom.: 4181 AF XY: 0.160 AC XY: 21681AN XY: 135160
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GnomAD4 exome AF: 0.207 AC: 302420AN: 1461266Hom.: 34198 Cov.: 33 AF XY: 0.202 AC XY: 146852AN XY: 726948
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GnomAD4 genome ? AF: 0.210 AC: 31872AN: 152038Hom.: 3651 Cov.: 32 AF XY: 0.202 AC XY: 15024AN XY: 74310
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Fraser syndrome 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at